Immunology of advancing disease among minorities with Multiple Sclerosis

少数族裔多发性硬化症进展性疾病的免疫学

• 批准号: 10629213
• 负责人: Lilyana Amezcua
• 金额: $ 53.65万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629213
• 关键词: Address; African American population; Antibodies; Antigen Targeting; Atrophic; B-Lymphocytes; Binding; Biological; Caring; Cells; Clinical; Data; Demyelinations; Disease; Disease Progression; Event; Face; Flow Cytometry; Frequencies; Future; Genes; Genetic; Goals; Health; Hispanic Populations; Immune; Immune response; Immunoglobulin G; Immunologics; Immunology; Incidence; Inflammation; Inflammatory; Knowledge; Latinx; Mediating; Minority; Minority Groups; Molecular Genetics; Multiple Sclerosis; Neurologic Deficit; Neurons; Oligoclonal Bands; Outcome; Patients; Plasmablast; Population; Positioning Attribute; Predisposition; Prevalence; Prevention; Production; Recovery; Refractory; Relapse; Reporting; Risk; Role; Severity of illness; Technology; Testing; advanced disease; clinical investigation; cognitive disability; cohort; diagnostic tool; disability; experience; gray matter; in vivo Model; indexing; insight; minority patient; minority subjects; mouse model; multiple sclerosis patient; neuroimmunology; neurotoxicity; next generation sequencing; novel; patient response; physically handicapped; predictive tools; tool; treatment response

PROJECT SUMMARY Greater disease severity and a more rapid disease progression is observed among US minority populations such as African Americans (AA) and Hispanics (Latinx) with Multiple Sclerosis (MS) compared to whites with MS. Despite these observations, very little data is available regarding the biological underpinnings resulting in this increased risk of unequivocal advancing disease among minorities with MS even though the incidence of MS disease is growing among minority populations. Further, there are concerns that AA and Latinx with MS are refractory to first-line therapies, which increases the concern that the poor outcomes reported reflect substandard care and treatment. Our long term goal is to facilitate prevention of neurological deficits in minority patients with MS by identifying the mechanism(s) of CNS inflammation contributing to intensified progression and severity of disease. Others have shown that minorities with MS display higher IgG index and synthesis rate, oligoclonal band positivity and an inverse correlation of IgG index with gray matter atrophy. These data support a pronounced role for B cells and their antibody products in the pathobiology of MS in minority populations. Our central hypothesis is that the underlying mechanism of unequivocal advancing disease among minorities with MS involves expansion of plasmablasts producing antibodies and/or inflammatory products that cause neuronal toxicity independent of genetic (i.e. ancestral) predispositions. These studies will provide novel mechanistic insights into the role of neuron-reactive plasmablasts in CNS inflammatory events associated with intensified progression and severity of disease in minorities with MS. Our findings will also support future studies to develop diagnostic and predictive tools that inform patient response to treatment and inform clinical course such as relapse of MS or progression to MS in minority populations.

项目摘要 在美国少数民族人群中观察到更严重的疾病和更快的疾病进展 例如患有多发性硬化症（MS）的非洲裔美国人（AA）和西班牙裔（Latinx）与患有多发性硬化症（MS）的白人相比， 女士尽管有这些观察结果，但关于导致死亡的生物基础的数据很少。 这增加了少数MS患者明确进展疾病的风险，尽管 多发性硬化症在少数群体中正在增长。此外，有人担心AA和Latinx与MS 一线治疗难治，这增加了对报告的不良结局反映的担忧。 低于标准的护理和治疗。 我们的长期目标是通过识别和治疗多发性硬化症， 中枢神经系统炎症导致疾病进展加剧和严重程度的机制。别人 少数MS患者IgG指数和合成率较高，寡克隆条带阳性， IgG指数与灰质萎缩呈负相关。这些数据支持了B细胞的显著作用 及其抗体产物在少数群体MS病理生物学中的作用。 我们的中心假设是，少数民族中明确的疾病进展的潜在机制 MS涉及浆母细胞的扩增，产生抗体和/或炎症产物， 神经毒性独立于遗传（即祖先）倾向。这些研究将提供新的 对神经元反应性浆母细胞在中枢神经系统炎症事件中作用的机制性认识 我们的研究结果也将支持未来的研究。 研究开发诊断和预测工具，告知患者对治疗的反应，并告知临床 例如MS复发或少数人群进展为MS。

项目成果

Inclusion of optic neuritis in dissemination in space improves the performance of McDonald 2017 criteria in Hispanic people with suspected multiple sclerosis.

将视神经炎纳入空间传播改善了疑似多发性硬化症西班牙裔患者的 McDonald 2017 标准的表现。

• DOI: 10.1177/13524585231209016
• 发表时间: 2023
• 期刊: Multiple sclerosis (Houndmills, Basingstoke, England)
• 作者: Amezcua,Lilyana;Robers,MichaelV;Soneji,Deepak;Manouvakhova,Olga;Martinez,Andrea;Islam,Talat
• 通讯作者: Islam,Talat